A large number of molecules having therapeutic activity, and especially anti-cancer molecules, have low solubility in water, owing to the intrinsic hydrophobic properties of the molecule. A certain level of hydrophobicity is in fact necessary for these molecules, in order to enable them to be internalised by cells. Vectorisation of therapeutic molecules is aimed at circumventing the problems associated with, especially, the solubility, stability, pharmacokinetics and biodistribution of said molecules and specifically targeting them.
Various vectorisation systems for hydrophobic compounds have been described in the literature as being capable of transporting sufficient amounts of molecules having therapeutic activity through the various biological barriers in order to efficaciously reach their site of action.
One of those vectorisation techniques consists of encapsulating an active ingredient in a microsphere formed by a matrix of polymers such as poly(alkylcyanoacrylates), poly(anhydrides) and polylactic acid). Those microspheres have sizes of from 20 μm to 100 μm, which rules out their use by the intravenous route and allows relatively low levels of inclusion of hydrophobic compounds of between 0.2% and 3.5%.
Polymer micelles, another vectorisation technique, denote colloidal dispersions composed of amphiphilic polymers having separate hydrophilic and hydrophobic regions. These polymer micelles are supramolecular core/shell structures. Polymer micelles are composed of polyethers used in combination with poly(ethylene glycol) in order to form amphiphilic polymers in the form of diblock copolymers (pluronics: PPO-co-PEG) or triblock copolymers (poloxamers: PEG-co-PPO-co-PEG). Those polymer micelles have a size between 50 nm and 100 nm. The inclusion levels of compounds in the polymer micelles are between 0.1% and 40%, inclusive, depending on the inclusion method used: inclusion by evaporation, inclusion by dialysis or inclusion by nanoprecipitation. Polymer micelles are accordingly vectors which allow large amounts of hydrophobic compounds to be incorporated but which require a difficult industrial and technical formation technique (synthesis and inclusion).
Vectorisation systems using liposomes and vesicles of polymers are the object of intensive research and a number of formulations of medicaments using these systems are currently undergoing clinical trials, some of them even having been approved for clinical use. Liposomes and vesicles of polymers may include hydrophilic active ingredients in the aqueous core of the vesicle or hydrophobic molecules in the polymer bilayer. Liposomes and vesicles of polymers have very varied structures (multi-lamellar vesicles MLV, small uni-lamellar vesicles SUV, large uni-lamellar vesicles LUV, giant vesicles GUV) and very varied sizes between 100 nm and 1000 nm, inclusive. Liposomes and vesicles of polymers are important active ingredient vehicles in the vectorisation of hydrophilic molecules.
In 2003, a new type of organisation on the surface of carbon nanotubes was discovered: nano-rings, i.e. a structuring of amphiphilics into rings over the entire length of the nanotubes. Nano-rings are rings of polymerised surfactants formed on the surface of the nanotubes and then separated from their carbon support in order to be used as solubilisation agents for hydrophobic active ingredients (WO 2004/092231). Nano-rings are, however, nano-vectors that are difficult to industrialize.
The above-described delivery vectors meet the challenge of vectorisation more or less well, which is to transport sufficient amounts of active ingredient in efficacious manner and with low toxicity in order to treat the pathology. These vectors remedy the problem of the solubility of hydrophobic active ingredients but without resolving the problems of vector size, formation and industrialization. The present invention is accordingly aimed at proposing a new strategy in order to obtain nano-vectors having a capability for inclusion of hydrophobic active ingredients that is greater than that of customary vectors in the literature and having a simple formulation facilitating their future industrialization.